Researchers unravel mystery and mechanism behind addiction

Chemical blockers can be used to inhibit the reward response triggered by addictive drugs.

May 2015

While it’s known that drug use has immediate short-term effects in the brain, what researchers don’t understand is why there can be long-term effects of drug use, even after just a single exposure. A new animal study out of the University of Calgary’s Hotchkiss Brain Institute (HBI) has revealed a mechanism responsible for this initial response to drugs, which is critical to the development of addiction.

Our brains are constantly making associations between various environmental cues and their predicted rewards; however, the problem with addiction is that these associations become abnormally strong — often leading to cravings and drug relapse in those trying to remain clean.

Addictive drugs tilt the brain’s reward scale off balance

“Addictive drugs, such as cocaine and nicotine, create an imbalance in important control mechanisms that regulate reward-linked regions, thereby tilting the scale so the significance of the drug outweighs everything else,” says Corey Baimel, a PhD student and an HBI trainee at the Cumming School of Medicine and lead author on the study. “We wanted to see if this was the case with opiate drugs, such as morphine, as well.”

The study, which was published earlier this month in The Journal of Neuroscience, looked at the neuropeptide orexin. Orexin, known for its role in regulating wakefulness and appetite, strengthens signaling in an area of the brain called the ventral tegmental area (VTA), which is critical for relaying information about environmental cues that predict rewards.

Study used signaling blockers to interfere with the reward response

Baimel and HBI member Stephanie Borgland, PhD, study co-author and assistant professor in the Department of Physiology and Pharmacology, gave a single exposure of morphine to animal models with or without an orexin signaling blocker. After 24 hours, they measured the strength of synapses (specialized sites of communication between neurons) to the VTA. In those that did not receive the blocker, it was observed that there was an increase in the strength of synapses between neurons — a mechanism linked to learning of the reward experience. In those that received the blocker, these strengthened synapses were not present, as though the drug had not been administered at all.

Borgland says this strengthening of synapses in the brain primes the user for a much bigger response during subsequent use, thereby creating even stronger associations to cues in the environment which has the potential to lead to addiction. In observing this mechanism, she hopes that this research could one day lead to treatments for those struggling with the illness.

“Treating addiction with medication isn’t a widely accepted practice” she says. “But if one day there’s a non-addictive drug, such as one that would block orexin signaling, to help treat addiction, I think that would be fantastic. There are a lot of addicts desperate for treatment.”

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